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Andréia C.K. Mortensen

Andréia C.K. Mortensen, PhD

Research Assistant Professor


Department: Pharmacology & Physiology

Education

  • PhD in Biochemistry - Ribeirão Preto School of Medicine, University of São Paulo, Brazil (2001)

Postgraduate Training / Additional Certifications

  • Postdoctoral Fellowship in Neuroscience – Vollum Institute, Oregon Health and Sciences University
  • Postdoctoral Associate in Neurobiology- University of Pittsburgh

Dr. Mortensen is a research assistant professor in the Department of Pharmacology & Physiology at Drexel University College of Medicine.

Research Overview

Our lab is interested in further the knowledge of mechanisms for regulation of glutamate transporters. We are highly interested in the identification and development of allosteric compounds that enhance their activity. Our goal is to target glutamate transporter subtype EAAT2 (the main glutamate transporter in the brain), for the development of approaches and compounds for neuroprotection in neurological disorders.

Visit the A. Mortensen Lab.

Research Interests

Glutamate transporters, neurological disorders and positive allosteric modulators that target transporters

Research

Excitatory amino acid transporters (EAATs) present on the plasma membrane regulate and modulate glutamate neurotransmission by removing synaptically released glutamate back into cells, thereby having a profound impact on the level of receptor activation.

The main goals of my research are to investigate the role of EAAT2, the main CNS astrocytic carrier, in neurodegenerative disorders including traumatic brain injury (TBI), ischemia, stroke, epilepsy and HIV-associated neurocognitive disorder (HAND), among others.

Molecules that limit glutamate release, antagonists of ionotropic glutamate receptors and compounds that target calcium influx have been demonstrated to reduce secondary effects of brain trauma. However, severe side effects limit their clinical use. In addition, compounds that enhance EAAT2 activity in pathological conditions, such as ß-lactam antibiotics, attenuate damage in both acute and chronic neurodegenerative disorders. However, this approach is best administered prophylactically and could be associated with non-specific effects that limit their utility

Spider venoms are a valuable source of compounds bioactive on synaptic transmission. We have discovered a unique natural compound from the spider Parawixia bistriata that increases the activity of glutamate transporter EAAT2 and has neuroprotective effect on retinal tissue from ischemic damage.

We have identified structural components that interact with this compound by using chimeras of EAAT2 and other subtypes of glutamate transporters. This unique information was used in virtual screening approaches to identify positive allosteric modulators of EAAT2. These novel compounds are being characterized in in vitro models of excitotoxicity and brain injury.

Our long-term goal is to progress our preclinical studies with this class of PAMs of EAAT2, by evaluating translational possibilities in in vivo models of neurological disorders, such as brain injury and epilepsy, and begin clinical trials in patients of relevant neurological disorders.

Publications

Selected Publications

"Current approaches to enhance glutamate transporter function and expression"
Fontana AC
J Neurochem. doi: 10.1111/jnc.13200, Jun 20, 2015

"Neuroprotective effects of the glutamate transporter activator, MS-153, following traumatic brain injury in the adult rat"
Fontana AC, Fox DP, Zoubroulis A, Mortensen OV, Raghupathi R
J Neurotrauma, Jul 22, 2015

"Molecular determinants of transport stimulation of EAAT2 are located at interface between the trimerization and substrate transport domains"
Mortensen OV, Liberato JL, Coutinho-Netto J, Dos Santos WF, Fontana AC
J Neurochem; 133(2):199-210. doi: 10.1111/jnc.13047 (Epub 2015 Feb 26) PubMed PMID: 25626691, April 2015

"The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA transporter activities"
Timple JM, Magalhães LG, Souza Rezende KC, Pereira AC, Cunha WR, Andrade e Silva ML, Mortensen OV, Fontana AC.
J Nat Prod.; 76(10):1889-95. doi: 10.1021/np400452n. (Epub 2013 Oct 10) Oct 25, 2013

"Identification of an allosteric modulator of the serotonin transporter with novel mechanism of action"
Kortagere S, Fontana AC, Rose DR, Mortensen OV
Neuropharmacology, 72:282-290. doi: 10.1016/j.neuropharm.2013.04.026, Sept 2013

"A catecholamine transporter from the human parasite Schistosoma mansoni with low affinity for psychostimulants"
Larsen MB, Fontana AC, Magallhães LG, Rodrigues V, Mortensen OV.
Mol Biochem Parasitol. Jan 18 2011

"Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin"
Fontana AC, Sonders MS, Pereira-Junior OS, Knight M, Javitch JA, Rodrigues V, Amara SG, Mortensen OV.
Eur J Pharmacol;616(1-3):48-57, Aug 15 2009

"Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom"
Fontana AC, de Oliveira Beleboni R, Wojewodzic MW, Ferreira Dos Santos W, Coutinho-Netto J, Grutle NJ, Watts SD, Danbolt NC, Amara SG.
Mol Pharmacol. 2007 Nov;72(5):1228-37. Epub Jul 23. 2007

"Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake"
Fontana AC, Guizzo R, de Oliveira Beleboni R, Meirelles E Silva AR, Coimbra NC, Amara SG, dos Santos WF, Coutinho-Netto.
J. Br J Pharmacol;139(7):1297-309, Aug 2003

"Excitatory amino acid transporters: keeping up with glutamate"
Amara SG, Fontana AC.
Neurochem Int;41(5):313-8. Review, Nov 2002


Contact Information


Research Office

Department of Pharmacology & Physiology
245 N. 15th Street
Mail Stop 488
Philadelphia, PA 19102
Phone: 215.762.4399
Fax: 215.762.2299